ORLANDO – An aggressive approach to treating early unfavorable Hodgkin’s lymphoma that combines the BEACOPP regimen at an escalated dose with the ABVD regimen and involved-field radiotherapy results in better tumor control than did ABVD and radiation alone, investigators have reported.
Dr. Andreas Engert
In the final analysis of the German Hodgkin Study Group (GHSG) HD14 trial, the estimated 5-year freedom-from-treatment-failure rate among patients treated with escalated-dose BEACOPP and ABVD plus radiotherapy (RT) was 94.3%, compared with 87.6% for those treated with ABVD/RT alone. The hazard ratio for BEACOPP/ABVD/RT was 0.49 (P =.0001), Dr. Peter Borchmann said at the annual meeting of the American Society of Hematology.
"We have this new treatment as the new standard of care at least in our studies. It will be challenged here in the U.S., because many doctors in the U.S., I guess, will still say ‘ABVD is the standard of care, and we don’t care about some 7% better tumor control at 5 years; we want to see overall survival differences.’ With this short follow-up we have now, there is no difference in overall survival," lead author Dr. Andreas Engert from University Hospital Cologne, Germany, said in a media briefing.
Although BEACOPP is associated with an increased risk for infertility, 18% of women up to age 40 years who were treated with the regimen reported having a pregnancy or giving birth more than 1 year after the end of therapy, compared with 11% treated with ABVD. Dr. Borchmann, also of University Hospital Cologne, said that all the women were able to conceive using their own eggs.
The GHSG HD14 trial compared four cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) with two cycles of escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) followed by two cycles of ABVD. In both treatment groups, chemotherapy was followed by involved field radiotherapy (IF-RT) at a dose of 30 Gy.
The patients had stage I or II disease with early unfavorable risk factors, including at least three involved lymph node areas, elevated erythrocyte sedimentation rate, large mediastinal mass, or extranodal disease. They were randomly assigned to either ABVD plus IF-RT in the control arm (818 patients) or BEACOPP/ABVD plus IF-RT in the experimental arm (805 patients). Patients were recruited from cancer centers and smaller oncology practices in Germany, Austria, Switzerland, the Czech Republic, and the Netherlands.
In July of 2008, the control arm was closed following an interim analysis that showed that the experimental arm had met the prespecified criteria for superiority.
An intention-to-treat analysis showed that both regimens had excellent tumor control, with 93.8% of patients in the control arm having complete responses (CR) or complete responses unconfirmed (CRu), compared with 94.5% of patients in the BEACOPP/ABVD arm. A total of 1.2% of patients in the control arm had partial responses, compared with 0.5% in the BEACOPP/ABVD arm. Relapses occurred in 8.1% and 2.6% of patients in the two arms, respectively.
Acute toxicities of either grade III or IV according to World Health Organization criteria occurred in 51% of patients on ABVD alone, and 87% of patients in the combination arm. Hematologic toxicities occurred in 24% and 80% and leukopenia with infections occurred in 1.2% and 9.8%, respectively.
In addition, there were no cases of acute myeloid leukemia or myelodysplasia among control patients, compared with three (0.4%) patients treated with BEACOPP/ABVD. Conversely, there were 10 cases of non-Hodgkin’s lymphoma (1.2%) among patients on ABVD alone, vs. 5 (0.6%) in those on BEACOPP/ABVD. Solid tumors occurred in nine (1.1%) and eight (1.0%) patients, respectively.
There were 20 deaths in each treatment arm. In the control arm, there were no deaths attributed to the study regimen and six deaths related to toxicity of the salvage regimen, compared with four and one, respectively, in the BEACOPP/ABVD arm. Secondary neoplasms were the cause of death in seven patients on ABVD alone, and three on BEACOPP/ABVD.
"I think it’s very reasonable to say that this regimen [BEACOPP/ABVD] regimen will become the new standard treatment for early unfavorable Hodgkin lymphoma patients. And I think this is a very strong chemotherapy background for the much more important question we are asking all over the world right now: Do we need combined modality treatment for these patients, or can we restrict radiotherapy to a subset of patients [with PET-positive residual disease]," Dr. Borchmann concluded.
The trial was supported by the German Cancer Aid fund. Dr. Borchmann and Dr. Engert had no conflict of interest disclosures.